For diseases based on acute hypoalbuminemia and chronic hypoalbuminemia which are hard to control, albumin preparations are used for improving clinical conditions by the supplementation thereof. Specifically, they are medical supplies indispensable for modern medical treatment because they are generally Used for correction of a circulating plasma volume in hemorrhagic and traumatic shock, improvement of edema, and various kinds of diseases such as liver cirrhosis and nephrotic syndrome (Peter T. Jr., The Plasma Proteins. Academic Press. New York. 133-81 (1975), Rosenorer V M., Rothschild M A., Albumin Structure, Function and Uses (1977)).
Conventionally, the production of human serum albumin preparations has been performed by fractionating blood collected from a human being and purifying the obtained albumin-containing aqueous solution according to various kinds of purification methods. The purification methods include an ethanol fractionation method, a PEG fractionation method, an ammonium sulfate fractionation method, a method in which the use of an anion exchanger is combined with heat treatment at 69° C. for 10 hours (JP 2-191226A), and a method in which treatment with an anion exchanger, treatment with a cation exchanger, and heat treatment at 60° C. for 10 hours are combined together (JP 3-17023A and JP 7-330626A) On the other hand, in recent years, the technology for mass production of albumin with a recombinant (gene recombination) has been established, and thus it has become possible to produce human albumin in large quantity by factory production without depending on blood donation (Clinical Molecular Medicine, 1, 939 (1993)).
In the production of albumin preparations (particularly, the production of fractionated human serum albumin), for removing a harmful virus unstable to heat and preventing contamination with a protein or the like, for example, a sterilization method such as low-temperature sterilization (60° C. for 10 hours) is used. In the low-temperature sterilization, N-acetyl tryptophan and sodium caprylate are added to human serum albumin (Ballou G A., Boyer P D., Luck J M., Lum F G., J. Biol. Chem., 153,589-605(1944), Scatchard G, Strong L E., Hughes W L. Jr., Ash Worth J N., Sparrow A H., J Clin. Invest., 24, 571-679 (1945), Boyer P D., Lum F G., Ballou G A., Luch J M., Rice R G., J.Biol. Chem., 162, 181-198 (1946)). However, the N-acetyl tryptophan has a side-effect problem such as intracerebral disease.
It is intended to provide albumin preparations with safety and without any risk of side effects, which are free from viruses or contaminating proteins and can be stably stored over a long time while showing neither changes in their appearance nor decrease in their content.